Previous work from this unit has focused on the cognitive and behavioral responses of Alzheimer patients to pharmacologic challenges with cholinergic and opiate antagonists. We observed that the dementia patients appeared more sensitive to these antagonists (scopolamine and naloxone) than previously reported in younger controls. This year, we have demonstrated that behavioral and cognitive responses (but not physiologic changes) following scopolamine are indeed greater at lower doses in Alzheimer patients than in age-matched controls, suggesting increased sensitivity in this population with known cholinergic deficits. We are now in the process of completing a similar comparison using naloxone in age-matched normal volunteers. Expanded studies of the cognitive, behavioral and neuroendocrine responses of Alzheimer patients to cholinergic agonists such as arecholine and nicotine are also underway.